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BACKGROUND: Identifying patients with COVID-19 disease who will deteriorate can be useful to assess whether they should receive intensive care, or whether they can be treated in a less intensive way or through outpatient care. In clinical care, routine laboratory markers, such as C-reactive protein, are used to assess a person's health status. OBJECTIVES: To assess the accuracy of routine blood-based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID-19 in people with SARS-CoV-2. SEARCH METHODS: On 25 August 2022, we searched the Cochrane COVID-19 Study Register, encompassing searches of various databases such as MEDLINE via PubMed, CENTRAL, Embase, medRxiv, and ClinicalTrials.gov. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of all designs that produced estimates of prognostic accuracy in participants who presented to outpatient services, or were admitted to general hospital wards with confirmed SARS-CoV-2 infection, and studies that were based on serum banks of samples from people. All routine blood-based laboratory tests performed during the first encounter were included. We included any reference standard used to define deterioration to severe or critical disease that was provided by the authors. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each included study, and independently assessed the methodological quality using the Quality Assessment of Prognostic Accuracy Studies tool. As studies reported different thresholds for the same test, we used the Hierarchical Summary Receiver Operator Curve model for meta-analyses to estimate summary curves in SAS 9.4. We estimated the sensitivity at points on the SROC curves that corresponded to the median and interquartile range boundaries of specificities in the included studies. Direct and indirect comparisons were exclusively conducted for biomarkers with an estimated sensitivity and 95% CI of ≥ 50% at a specificity of ≥ 50%. The relative diagnostic odds ratio was calculated as a summary of the relative accuracy of these biomarkers. MAIN RESULTS: We identified a total of 64 studies, including 71,170 participants, of which 8169 participants died, and 4031 participants deteriorated to severe/critical condition. The studies assessed 53 different laboratory tests. For some tests, both increases and decreases relative to the normal range were included. There was important heterogeneity between tests and their cut-off values. None of the included studies had a low risk of bias or low concern for applicability for all domains. None of the tests included in this review demonstrated high sensitivity or specificity, or both. The five tests with summary sensitivity and specificity above 50% were: C-reactive protein increase, neutrophil-to-lymphocyte ratio increase, lymphocyte count decrease, d-dimer increase, and lactate dehydrogenase increase. Inflammation For mortality, summary sensitivity of a C-reactive protein increase was 76% (95% CI 73% to 79%) at median specificity, 59% (low-certainty evidence). For deterioration, summary sensitivity was 78% (95% CI 67% to 86%) at median specificity, 72% (very low-certainty evidence). For the combined outcome of mortality or deterioration, or both, summary sensitivity was 70% (95% CI 49% to 85%) at median specificity, 60% (very low-certainty evidence). For mortality, summary sensitivity of an increase in neutrophil-to-lymphocyte ratio was 69% (95% CI 66% to 72%) at median specificity, 63% (very low-certainty evidence). For deterioration, summary sensitivity was 75% (95% CI 59% to 87%) at median specificity, 71% (very low-certainty evidence). For mortality, summary sensitivity of a decrease in lymphocyte count was 67% (95% CI 56% to 77%) at median specificity, 61% (very low-certainty evidence). For deterioration, summary sensitivity of a decrease in lymphocyte count was 69% (95% CI 60% to 76%) at median specificity, 67% (very low-certainty evidence). For the combined outcome, summary sensitivity was 83% (95% CI 67% to 92%) at median specificity, 29% (very low-certainty evidence). For mortality, summary sensitivity of a lactate dehydrogenase increase was 82% (95% CI 66% to 91%) at median specificity, 60% (very low-certainty evidence). For deterioration, summary sensitivity of a lactate dehydrogenase increase was 79% (95% CI 76% to 82%) at median specificity, 66% (low-certainty evidence). For the combined outcome, summary sensitivity was 69% (95% CI 51% to 82%) at median specificity, 62% (very low-certainty evidence). Hypercoagulability For mortality, summary sensitivity of a d-dimer increase was 70% (95% CI 64% to 76%) at median specificity of 56% (very low-certainty evidence). For deterioration, summary sensitivity was 65% (95% CI 56% to 74%) at median specificity of 63% (very low-certainty evidence). For the combined outcome, summary sensitivity was 65% (95% CI 52% to 76%) at median specificity of 54% (very low-certainty evidence). To predict mortality, neutrophil-to-lymphocyte ratio increase had higher accuracy compared to d-dimer increase (RDOR (diagnostic Odds Ratio) 2.05, 95% CI 1.30 to 3.24), C-reactive protein increase (RDOR 2.64, 95% CI 2.09 to 3.33), and lymphocyte count decrease (RDOR 2.63, 95% CI 1.55 to 4.46). D-dimer increase had higher accuracy compared to lymphocyte count decrease (RDOR 1.49, 95% CI 1.23 to 1.80), C-reactive protein increase (RDOR 1.31, 95% CI 1.03 to 1.65), and lactate dehydrogenase increase (RDOR 1.42, 95% CI 1.05 to 1.90). Additionally, lactate dehydrogenase increase had higher accuracy compared to lymphocyte count decrease (RDOR 1.30, 95% CI 1.13 to 1.49). To predict deterioration to severe disease, C-reactive protein increase had higher accuracy compared to d-dimer increase (RDOR 1.76, 95% CI 1.25 to 2.50). The neutrophil-to-lymphocyte ratio increase had higher accuracy compared to d-dimer increase (RDOR 2.77, 95% CI 1.58 to 4.84). Lastly, lymphocyte count decrease had higher accuracy compared to d-dimer increase (RDOR 2.10, 95% CI 1.44 to 3.07) and lactate dehydrogenase increase (RDOR 2.22, 95% CI 1.52 to 3.26). AUTHORS' CONCLUSIONS: Laboratory tests, associated with hypercoagulability and hyperinflammatory response, were better at predicting severe disease and mortality in patients with SARS-CoV-2 compared to other laboratory tests. However, to safely rule out severe disease, tests should have high sensitivity (> 90%), and none of the identified laboratory tests met this criterion. In clinical practice, a more comprehensive assessment of a patient's health status is usually required by, for example, incorporating these laboratory tests into clinical prediction rules together with clinical symptoms, radiological findings, and patient's characteristics.

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BACKGROUND: Diagnostic testing is prevalent among children with persistent non-specific symptoms (PNS), and both undertesting and overtesting have negative consequences for child and society. Research in adults with PNS has shown that general practitioners (GPs) use diagnostic testing for reasons other than diagnosis, but comparable research has not been conducted in children. Understanding GPs' perspectives of testing decisions in children could provide insights into mechanisms of undertesting and overtesting. AIM: To investigate GPs' perspectives of conducting or refraining from diagnostic testing in children with PNS, and differences with motives in adults. DESIGN AND SETTING: Qualitative study using semi-structured interviews with Dutch GPs. METHOD: We purposively sampled GPs until data saturation. Reasons for conducting or refraining from diagnostic tests were explored using two real-life cases from daily practice. Online video interviews were transcribed verbatim. Data were collected and analyzed concurrently by thematic content analysis. FINDINGS: Twelve GPs participated. Their decision-making involved a complex trade-off among four themes: medical (e.g., alarm symptoms), psychosocial (e.g., doctor-patient relationship), consultation management (e.g., 'quick fix'), and efficient resource utilization (e.g., sustainability). Compared to adults, GPs were more hesitant to conduct diagnostic testing in children due to their higher vulnerability to fearing invasive procedures, lower probability of organic disease, and reduced autonomy. CONCLUSION: As in adults, GPs' decisions to conduct diagnostic tests in children were motivated by reasons beyond diagnostic uncertainty. Educational programs, interventions, and guidelines that aim to change the testing behaviors of GPs in children with PNS should target these reasons as well.

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OBJECTIVES: This study aims to investigate C reactive protein (CRP) testing practices in paediatric ambulatory care across British primary care and accident and emergency (A&E) departments. DESIGN, SETTING, PARTICIPANTS: This retrospective cohort study included children <18 years old having ≥1 CRP test at primary care or A&E departments in Oxfordshire between 2007 and 2021. OUTCOMES: We estimated the frequency and annual changes in CRP testing in both settings and evaluated referral and admission patterns based on CRP levels: low (<20 mg/L), intermediate or high (≥80 mg/L). RESULTS: Over 15 years, 91 540 CRP tests were requested in 63 226 children, with 33 882 (53.6%) in primary care and 29 344 (46.4%) in A&E. Both settings showed rising trends in test requests, with average annual percentage change of 3.0% (95% CI 1.2% to 4.7%) in primary care and 11.5% (95% CI 8.6% to 14.6%) in A&E. The proportion of intermediate/high-test results remained stable. In primary care, 50 709 (95.8%) of CRP tests were <20 mg/L, with 99.0% of these children managed at home. High and intermediate CRP values increased odds of referral versus low CRP (OR adjusted for age=21.80; 95% CI 16.49 to 28.81 and 4.77; 3.78 to 6.02, respectively). At A&E, 27 610 (71.5%) children had CRP<20 mg/L, of whom 42.5% were admitted while 3776 (9.8%) had CRP≥80 mg/L with 57.9% admission rate. High and intermediate CRP values increased odds of admission versus low CRP (OR adjusted for age=1.90; 95% CI 1.78 to 2.04 and 1.39; 1.32 to 1.46, respectively). CONCLUSION: There are rising trends of CRP test requests in paediatric ambulatory care settings, with no evidence of increases in proportion of intermediate/high-test results in primary care. Low CRP values at primary care were linked to children managed at home, while almost half of children with low CRP values at A&E were admitted to the hospital.

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BACKGROUND: Recognition of acute diverticulitis is important to determine an adequate management strategy. Differentiating it from other gastrointestinal disorders is challenging as symptoms overlap. Clinical tests might assist the clinician with this diagnostic challenge. Previous reviews have focussed on prognostic questions and imaging examinations in secondary care. OBJECTIVE: To evaluate the diagnostic accuracy of clinical tests feasible in primary care for acute diverticulitis in suspected patients. METHOD: We have systematically searched multiple databases for diagnostic accuracy studies of tests feasible in primary care compared to a reference standard in suspected patients. Two reviewers independently selected studies, extracted data, and assessed study quality with the QUADAS-2 tool. We have meta-analysed the results in the case of more than four studies per index test. RESULTS: Seventeen studies were included, all studies were performed in secondary care (median prevalence 48%). Individual signs and symptoms showed a wide range in sensitivity (range 0.00-0.98) and specificity (range 0.08-1.00). Of the four laboratory tests evaluated, CRP >10 mg/l had the highest sensitivity (range 0.89-0.96) with specificity ranging from 0.28 to 0.61. Ultrasound had the highest pooled sensitivity and specificity of 0.92 (95% CI 0.86-0.96) and 0.94 (95% CI 0.88-0.97), respectively. CONCLUSION: None of the studies were performed in primary care. Individual signs and symptoms alone are insufficiently informative for acute diverticulitis diagnosis. CRP showed potential for ruling out and ultrasound had a high diagnostic accuracy. More research is needed about the diagnostic accuracy of these tests in primary care. PROSPERO REGISTRATION NUMBER: CRD42021230622.

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Individual participant-data meta-analysis (IPDMA) uses data at the participant level to synthesize evidence on clinical decision-making. We discuss the differences from aggregate-data meta-analysis and the advantages and challenges of IPDMA. IPDMA provides an opportunity to study effect modifiers at the participant level and can reduce bias in comparison to aggregate-data meta-analysis. A challenge with IPDMA is that it often requires considerable effort to obtain all the data, and an inability to obtain data for all the studies can lead to availability bias. PATIENT SUMMARY: Systematic reviews of the literature are performed to summarize available evidence regarding clinical decisions. Here we explain the differences between reviews that use aggregated data from published studies and reviews that use the participant-level data from those studies.

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BACKGROUND: For diagnostic research on appendicitis in registration data, insight is needed in the way GPs generate medical records. We aimed to reach a consensus on the features that GPs consider important in the consultation and medical records when evaluating a child with suspected appendicitis. METHODS: We performed a three-round Delphi study among Dutch GPs selected by purposive sampling. An initial feature list was created based on a literature search and features in the relevant Dutch guideline. Finally, using a vignette describing a child who needed later reassessment, we asked participants to complete an online questionnaire about which consultation features should be addressed and recorded. RESULTS: A literature review and Dutch guideline yielded 95 consultation features. All three rounds were completed by 22 GPs, with the final consensus list containing 26 symptoms, 29 physical assessments and signs, 2 additional tests, and 8 further actions (including safety-netting, i.e., informing the patient about when to contact the GP again). Of these, participants reached consensus that 37 should be actively addressed and that 20 need to be recorded if findings are negative. CONCLUSIONS: GPs agreed that negative findings do not need to be recorded for most features and that records should include the prognostic and safety-netting advice given. The results have implications in three main domains: for research, that negative findings are likely to be missing; for medicolegal purposes, that documentation cannot be expected to be complete; and for clinical practice, that safety-netting advice should be given and documented.

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BACKGROUND: In care substitution services, medical specialists offer brief consultations to provide general practitioners (GPs) with advice on diagnosis, treatment, or hospital referral. When GPs serve as gatekeepers to secondary care, these regional services could reduce pressures on healthcare systems. The aim is to determine the impact of implementing a care substitution service for dermatology, orthopaedics, and cardiology on the hospital referral rate, health care costs, and patient satisfaction. METHODS: A before-after study was used to evaluate hospital referral rates and health care costs during a follow-up period of 1 year. The study population comprised patients with eligible International Classification of Primary Care codes for referral to the care substitution service (only dermatology, orthopaedic, cardiology indications), as pre-defined by GPs and medical specialists. We compared referral rates before and after implementation by χ2 tests and evaluated patient preference by qualitative analysis. RESULTS: In total, 4,930 patients were included, 2,408 before and 2,522 after implementation. The care substitution service decreased hospital referrals during the follow-up period from 15 to 11%. The referral rate decreased most for dermatology (from 15 to 9%), resulting in a cost reduction of €10.59 per patient, while the other two specialisms experienced smaller reductions in referral rates. Patients reported being satisfied, mainly because of the null cost, improved organisation, improved care, and positive experience of the consultation. CONCLUSIONS: The care substitution service showed promise for specialisms that require fewer hospital facilities, as exemplified by dermatology.

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PURPOSE: Acute gastroenteritis is a common infectious disease in children younger than 6 years of age. Although it is a self-limiting disease, it nevertheless has a high consultation rate in primary care, especially during out-of-hours primary care (OOH-PC). Reasons for this high consultation rate remain unclear. METHODS: The aim of this qualitative study was to explore parental motivations, expectations, and experiences of OOH-PC contacts for children with acute gastroenteritis. We conducted 14 semistructured interviews with parents who contacted OOH-PC in the Netherlands. Interviews were audio-recorded, transcribed, and analyzed using elements of grounded theory and a constant-comparison approach. RESULTS: Unusual behavior of the sick child, absent micturition, and ongoing vomiting and/or diarrhea, with decreased or no fluid intake, motivated parents to contact OOH-PC. Parents initiated contact to prevent symptom deterioration and to be reassured by a general practitioner (GP), expecting them to perform a thorough physical examination, provide information, and make follow-up plans. Parents reported dissatisfaction if they felt unheard, misunderstood, or not taken seriously, and this increased their likelihood of seeking another consultation. General practitioners did not always meet parental expectations. CONCLUSION: Multiple factors affect the decision for parents to contact OOH-PC for their child with gastroenteritis. There is a mismatch between parental expectations and actions of the GP. Awareness regarding parental feelings and understanding their expectations can guide GPs in the interaction with parents, which could improve satisfaction with primary health care and OOH-PC specifically.

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BACKGROUND: Recognising acute appendicitis in children presenting with acute abdominal pain in primary care is challenging. General practitioners (GPs) may benefit from a clinical prediction rule. OBJECTIVES: To develop and validate a clinical prediction rule for acute appendicitis in children presenting with acute abdominal pain in primary care. METHODS: In a historical cohort study data was retrieved from GP electronic health records included in the Integrated Primary Care Information database. We assigned children aged 4-18 years presenting with acute abdominal pain (≤ 7 days) to development (2010-2012) and validation (2013-2016) cohorts, using acute appendicitis within six weeks as the outcome. Multiple logistic regression was used to develop a prediction model based on predictors with > 50% data availability derived from existing rules for secondary care. We performed internal and external temporal validation and derived a point score to stratify risk of appendicitis into three groups, i.e. low-risk, medium-risk and high-risk. RESULTS: The development and validation cohorts included 2,041 and 3,650 children, of whom 95 (4.6%) and 195 (5.3%) had acute appendicitis. The model included male sex, pain duration (<24, 24-48, > 48 h), nausea/vomiting, elevated temperature (≥ 37.3 °C), abnormal bowel sounds, right lower quadrant tenderness, and peritoneal irritation. Internal and temporal validation showed good discrimination (C-statistics: 0.93 and 0.90, respectively) and excellent calibration. In the three groups, the risks of acute appendicitis were 0.5%, 7.5%, and 41%. CONCLUSION: Combined with further testing in the medium-risk group, the prediction rule could improve clinical decision making and outcomes.

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BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in children. However, in primary care, it is still unknown whether there are differences in the prognosis of children with IBS compared to other diagnostic subgroups. Therefore, our aim was to describe the course of symptoms and health-related quality of life (HRQoL) for children with chronic gastrointestinal symptoms who either do or do not fulfil the Rome criteria for IBS in primary care. Second, we compared the diagnosis of the general practitioner (GP) with the Rome criteria. METHODS: We conducted a prospective cohort study with 1-year follow-up, including children aged 4-18 years with chronic diarrhoea and/or chronic abdominal pain in primary care. During follow-up, the Rome III questionnaire, Child Health Questionnaire, and symptom questionnaires were completed. RESULTS: A total of 60/104 children (57.7%) fulfilled the Rome criteria for IBS at baseline. Compared to children without IBS, children with IBS were more commonly referred to secondary care, used more laxatives, and more often developed chronic diarrhoea and low physical HRQoL during 1 year. The diagnosis "IBS" from the GP matched the Rome criteria for only 10% of children, as most were diagnosed with "Constipation." CONCLUSIONS: There seems to be a difference in the treatment and prognosis of symptoms and HRQoL between children with and without IBS in primary care. This suggests that it is relevant to differentiate between these groups. The evaluation and use of feasible criteria to define IBS in different healthcare settings remains subject for further studies.

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OBJECTIVE: To describe the testing, prescription, referral, and follow-up management by general practitioners (GPs) for children presenting with non-acute abdominal pain and/or diarrhea in primary care. DESIGN: Retrospective cohort study with one-year follow-up. SETTING: Registry data from a Dutch primary care database (AHON) between 2015 and 2019. SUBJECTS: Children aged 4-18 years old who presented by face-to-face consultation in primary care for non-acute abdominal pain and/or diarrhea (>7 days). MAIN OUTCOME MEASURES: We recorded the proportions of children who received (1) diagnostic testing, medicine prescriptions, follow-up consultations, and referrals at their first visit and (2) repeat consultations and referrals by one-year of follow-up. RESULTS: Among the 2200 children (median age, 10.5 years; interquartile range, 7.0-14.6) presenting to a GP with non-acute abdominal pain and/or diarrhea, most reported abdominal pain (78.7%). At the first visit, GPs performed diagnostic testing for 32.2%, provided a prescription to 34.5%, and referred 2.5% to secondary care. Twenty-five percent of the children had a follow-up consultation within four weeks and 20.8% had a repeat consultation between four weeks and one year. Thirteen percent of the children were referred to secondary care by one year. However, only 1% of all children had documentation of an organic diagnosis needing management in secondary care. CONCLUSION: One-third of children received diagnostic testing or a medicine prescription. Few had a follow-up consultation and >10% was referred to pediatric care. Future research should explore the motivations of GPs why and which children receive diagnostic and medical interventions.

General practitioners (GPs) often manage children with non-acute abdominal pain and/or diarrhea, which is typically due to a functional gastrointestinal disorder (FGID).Nearly one-third of all children underwent diagnostic testing at their first visit.Although recommended by the guideline of the Dutch Society of GPs, we found that only a quarter of children received a follow-up consultation.Thirteen percent of children were referred to pediatric specialist care by one year.

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OBJECTIVES: Chronic gastrointestinal symptoms are common among children and affect their daily activities and quality of life. The majority will be diagnosed with a functional gastrointestinal disorder. Effective reassurance and education are, therefore, key components of the physician's management. Qualitative studies have shown how parents and children experience specialist paediatric care, yet less is known about general practitioners (GPs), who manage most cases in the Netherlands and have a more personal and enduring relationship with their patients. Therefore, this study evaluates the expectations and experiences of parents of children visiting a GP for chronic gastrointestinal symptoms. DESIGN: We conducted a qualitative interview study. Online interviews were audio and video recorded, transcribed verbatim and independently analysed by the first two authors. Data were collected and analysed concurrently until data saturation was reached. Using thematic analysis, we developed a conceptual framework reflecting respondent expectations and experiences. We performed a member check of the interview synopsis and the conceptual framework. SETTING: Dutch primary care. PARTICIPANTS: We purposively sampled participants from a randomised controlled trial evaluating the effectiveness of faecal calprotectin testing in children with chronic gastrointestinal complaints in primary care. Thirteen parents and two children participated. RESULTS: Three key themes emerged: disease burden, GP-patient relationship and reassurance. Often, the experienced disease burden and the pre-existing GP-patient relationship influenced expectations (eg, for further investigations or a sympathetic ear), and when a GP fulfilled these expectations, a trusting GP-patient relationship ensued that facilitated reassurance. We found that individual needs influenced these themes and their interrelationships. CONCLUSION: Insights provided by this framework could help GPs managing children with chronic gastrointestinal symptoms in daily practice and may therewith improve the consultation experience for parents. Further research should evaluate whether this framework also holds true for children. TRIAL REGISTRATION NUMBER: NL7690.

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OBJECTIVE: Possible childhood appendicitis is a common emergency presentation. The exact value of blood tests is debated. This study sought to determine the diagnostic accuracy of four blood tests (white cell count (WCC), neutrophil(count or percentage), C reactive protein (CRP) and/or procalcitonin) for childhood appendicitis. DESIGN: A systematic review and diagnostic meta-analysis. Data sources included MEDLINE, EMBASE, Central, Web of Science searched from inception-March 2022 with reference searching and authors contacted for missing/unclear data. Eligibility criteria was studies reporting the diagnostic accuracy of the four blood tests compared to the reference standard (histology or follow-up). Risk of bias was assessed (QUADAS-2), pooled sensitivity and specificity were generated for each test and commonly presented cut-offs. To provide insight into clinical impact, we present strategies using a hypothetical cohort. RESULTS: 67 studies were included (34 839 children, 13 342 with appendicitis), all in the hospital setting. The most sensitive tests were WCC (≥10 000 cells/µL, 53 studies sensitivity 0.85 (95% CI 0.80 to 0.89)) and absolute neutrophil count (ANC) (≥7500 cells/µL, five studies sensitivity 0.90 (95% CI 0.85 to 0.94)). Combination of WCC or CRP increased sensitivity further(≥10 000 cells/µL or ≥10 mg/L, individual patient data (IPD) of 6 studies, 0.97 (95% CI 0.93 to 0.99)).Applying results to a hypothetical cohort(1000 children with appendicitis symptoms, of whom 400 have appendicitis) 60 and 40 children would be wrongly discharged based solely on WCC and ANC, respectively, 12 with combination of WCC or CRP.The most specific tests were CRP alone (≥50 mg/L, 38 studies, specificity 0.87 (95% CI 0.80 to 0.91)) or combined with WCC (≥10 000 cells/µL and ≥50 mg/L, IPD of six studies, 0.93 (95% CI 0.91 to 0.95)). CONCLUSIONS: The best performing single blood tests for ruling-out paediatric appendicitis are WCC or ANC; with accuracy improved combining WCC and CRP. These tests could be used at the point of care in combination with clinical prediction rules. We provide insight into the best cut-offs for clinical application. PROSPERO REGISTRATION NUMBER: CRD42017080036.

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BACKGROUND: The aim of this article is to describe the courses of vomiting, diarrhea, fever, and clinical deterioration, in children with uncomplicated gastroenteritis at presentation. This study was performed as a 7-day prospective follow-up study in an out-of-hours primary care service. The course of vomiting, diarrhea, and fever was analyzed by generalized linear mixed modeling. Because young children (≤ 12 months) and children with severe vomiting are at increased risk of dehydration, the potentially more complicated courses of these groups are described separately. The day(s) most frequently associated with deterioration and the symptoms present in children who deteriorated during follow-up were also described. RESULTS: In total, 359 children presented with uncomplicated acute gastroenteritis to the out-of-hours primary care service. Of these, 31 (8.6%) developed a complicated illness and needed referral or hospitalization. All symptoms decreased within 5 days in most children (> 90%). Vomiting and fever decreased rapidly, but diarrhea decreased at a somewhat slower pace, especially among children aged 6-12 months. Children who deteriorated during follow-up had a higher frequency of vomiting at presentation and higher frequencies of vomiting and fever during follow-up. CONCLUSIONS: The frequency of vomiting, not its duration, appears to be the more important predictor of deterioration. When advising parents, it is important to explain the typical symptom duration and to focus on alarm symptoms. Clinicians should be vigilant for children with higher vomiting frequencies at presentation and during follow-up because these children are more likely to deteriorate.

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BACKGROUND: The diagnostic value of C-reactive protein (CRP) for appendicitis in children has not been evaluated in primary care. As biochemical responses and differential diagnoses vary with age, separate evaluation in children and adults is needed. OBJECTIVES: To determine whether adding CRP to symptoms and signs improves the diagnosis of appendicitis in children with acute abdominal pain in primary care. METHODS: A retrospective cohort study in Dutch general practice. Data was collected from the Integrated Primary Care Information database between 2010 and 2016. We included children aged 4-18 years, with no history of appendicitis, presenting with acute abdominal pain, and having a CRP test. Initial CRP levels were related to the specialist's diagnosis of appendicitis, and the test's characteristics were calculated for multiple cut-offs. The value of adding CRP to signs and symptoms was analysed by logistic regression. RESULTS: We identified 1076 eligible children, among whom 203 were referred for specialist evaluation and 70 had appendicitis. The sensitivity and specificity of a CRP cut-off ≥10 mg/L were 0.87 (95%CI, 0.77-0.94) and 0.77 (95%CI, 0.74-0.79), respectively. When symptoms lasted > 48 h, this sensitivity increased to 1.00. Positive predictive values for CRP alone were low (0.18-0.38) for all cut-off values (6-100 mg/L). Adding CRP increased the area under the curve from 0.82 (95%CI, 0.78-0.87) to 0.88 (95%CI, 0.84-0.91), and decision curve analysis confirmed that its addition provided the highest net benefit. CONCLUSION: CRP adds value to history and physical examination when diagnosing appendicitis in children presenting acute abdominal pain in primary care. Appendicitis is least likely if the CRP value is < 10 mg/L and symptoms have been present for > 48 h.

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OBJECTIVE: Health care expenditures for children with functional constipation (FC) are high, while conservative management is successful in only 50% of the children. The aim is to evaluate whether adding physiotherapy to conventional treatment (CT) is a cost-effective strategy in the management of children with FC aged 4-18 years in primary care. METHODS: A cost-effectiveness analysis was performed alongside a randomized controlled trial (RCT) with 8-month follow-up. Costs were assessed from a societal perspective, effectiveness included both the primary outcome (treatment success defined as the absence of FC and no laxative use) and the secondary outcome (absence of FC irrespective of laxative use). Uncertainty was assessed by bootstrapping and cost-effectiveness acceptability curves (CEACs) were displayed. RESULTS: One hundred and thirty-four children were randomized. The incremental cost-effectiveness ratio (ICER) for one additional successfully treated child in the physiotherapy group compared with the CT group was €24,060 (95% confidence interval [CI] €-16,275 to €31,390) and for the secondary outcome €1,221 (95% CI €-12,905 to €10,956). Subgroup analyses showed that for children with chronic laxative use the ICER was €2,134 (95% CI -24,975 to 17,192) and €571 (95% CI 11 to 3,566), respectively. At a value of €1,000, the CEAC showed a probability of 0.53 of cost-effectiveness for the primary outcome, and 0.90 for the secondary outcome. CONCLUSIONS: Physiotherapy added to CT as first-line treatment for all children with FC is not cost-effective compared with CT alone. Future studies should consider the cost-effectiveness of physiotherapy added to CT in children with chronic laxative use. TRIAL REGISTRATION: The RCT is registered in the Netherlands Trial Register (NTR4797), on the 8th of September 2014. The first child was enrolled on the 2nd of December 2014. https://www.trialregister.nl/trial/4654.

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BACKGROUND: Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. AIM: To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. METHOD: Children were included if they were: aged 6 months-6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). CONCLUSION: Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine.

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BACKGROUND: General practitioners (GPs) face a diagnostic challenge when assessing acute abdominal pain in children. However, no information is available on the current diagnostic process or the diagnostic accuracy of history and physical examination in primary care settings. OBJECTIVE: To describe the diagnostic process for acute abdominal pain among children in primary care, focusing on appendicitis, and to assess the diagnostic accuracy of individual clinical features. METHODS: A retrospective cohort study in Dutch primary care, using the Integrated Primary Care Information database. Children aged 4-18 years were included if they had no history of appendicitis and presented with acute abdominal pain during 2010-2016. We evaluated GP management and the diagnostic accuracy of clinical features for appendicitis. Pre- and post-test probabilities were calculated for each clinical feature and compared with the probability of appendicitis after GP assessment. RESULTS: Out of 5691 children, 944 (16.6%) were referred and 291 (5.1%) had appendicitis, of whom 55 (18.9%) were initially misdiagnosed. The pre-test probability (i.e. of appendicitis in evaluated children) varied from 3% (rigidity) to 28% (migratory pain). Concerning post-test probabilities, positive values for rebound pain (32.1%) and guarding (35.8%) and the negative value for right lower quadrant tenderness (0.6%) were superior to overall GP assessment (29.6% and 1.1%, respectively). CONCLUSIONS: GP assessment will miss almost one-fifth of children with appendicitis at their first presentation, and about two-third of GP referrals will be negative. The presence of specific signs can increase or decrease the likelihood of appendicitis, emphasising the importance of a physical examination.

It can be difficult for general practitioners (GPs) to assess acute abdominal pain in children because they must decide whether it is a common minor problem or an uncommon serious problem. However, unlike their hospital counterparts, GPs must often rely on only the history and examination. We, therefore, wanted to gain a better understanding of how GPs assess abdominal pain and the accuracy of the different parts of their assessment. To do this, we looked back at clinical records for children who presented to a GP with acute abdominal pain between 2010 and 2016. The effect of examination on the probability of detecting appendicitis was calculated for several clinical features, and these were compared with the probability of appendicitis after a full GP assessment. Approximately 1 in 20 of the included children was diagnosed with appendicitis, one in five were initially misdiagnosed, and one in four were ultimately referred to the hospital. We show that some signs and symptoms were not particularly useful for assessment, but when they were, signs detected by the GP examining the patient were more useful than symptoms reported by patients or parents. We recommend that GPs provide safety netting advice and examine the abdomen.

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